Suspected Iatrogenic Seeding of Oral Melanoma Secondary to Endotracheal Intubation in a Dog.

A 10 yr old castrated male pug was presented with a 3 day history of intermittent dyspnea, cough, inappetence, and inability to breathe while sleeping. He had previously received hypofractionated radiation therapy for an amelanotic oral malignant melanoma (OMM) 7 mo prior to presentation. At presentation, the dog was gasping and dyspneic. Oral examination identified the OMM on the right hard palate. Thoracic radiographs revealed an angular soft-tissue opacity within the trachea just distal to the thoracic inlet. No evidence of pulmonary metastatic disease was seen. Tracheoscopy identified a pedunculated, nonpigmented mass within the lumen of the distal trachea near the carina. Treatment options were presented to the owners and included tracheal stenting or tracheal resection and anastomosis. Because of the poor prognosis, the owners elected humane euthanasia. Postmortem examination confirmed the presence of melanoma in the distal trachea; no other sites of OMM metastasis were identified. The cause of OMM development in the distal trachea in this case is suspected to have resulted from mechanical tumor cell seeding during endotracheal tube placement for general anesthesia 7 mo prior to presentation. Despite the reported rarity of mechanical tumor seeding, this potential complication warrants consideration in dogs with OMM.

The N-terminal Helical Region of the Hepatitis C Virus p7 Ion Channel Protein Is Critical for Infectious Virus Production.

The hepatitis C virus (HCV) p7 protein is required for infectious virus production via its role in assembly and ion channel activity. Although NMR structures of p7 have been reported, the location of secondary structural elements and orientation of the p7 transmembrane domains differ among models. Furthermore, the p7 structure-function relationship remains unclear. Here, extensive mutagenesis, coupled with infectious virus production phenotyping and molecular modeling, demonstrates that the N-terminal helical region plays a previously underappreciated yet critical functional role, especially with respect to E2/p7 cleavage efficiency. Interrogation of specific N-terminal helix residues identified as having p7-specific defects and predicted to point toward the channel pore, in a context of independent E2/p7 cleavage, further supports p7 as a structurally plastic, minimalist ion channel. Together, our findings indicate that the p7 N-terminal helical region is critical for E2/p7 processing, protein-protein interactions, ion channel activity, and infectious HCV production.

Hepatitis C virus infects rhesus macaque hepatocytes and simianized mice.

UNLABELLED: At least 170 million people are chronically infected with hepatitis C virus (HCV). Owing to the narrow host range of HCV and restricted use of chimpanzees, there is currently no suitable animal model for HCV pathogenesis studies or the development of a HCV vaccine. To identify cellular determinants of interspecies transmission and establish a novel immunocompetent model system, we examined the ability of HCV to infect hepatocytes from a small nonhuman primate, the rhesus macaque (Macaca mulatta). We show that the rhesus orthologs of critical HCV entry factors support viral glycoprotein-dependent virion uptake. Primary hepatocytes from rhesus macaques are also permissive for HCV-RNA replication and particle production, which is enhanced when antiviral signaling is suppressed. We demonstrate that this may be owing to the diminished capacity of HCV to antagonize mitochondrial antiviral-signaling protein-dependent innate cellular defenses. To test the ability of HCV to establish persistent replication in vivo, we engrafted primary rhesus macaque hepatocytes into immunocompromised xenorecipients. Inoculation of resulting simian liver chimeric mice with either HCV genotype 1a or 2a resulted in HCV serum viremia for up to 10 weeks. CONCLUSION: Together, these data indicate that rhesus macaques may be a viable model for HCV and implicate host immunity as a potential species-specific barrier to HCV infection. We conclude that suppression of host immunity or further viral adaptation may allow robust HCV infection in rhesus macaques and creation of a new animal model for studies of HCV pathogenesis, lentivirus coinfection, and vaccine development.

Associations between meniscal tears and various degrees of osteoarthritis among dogs undergoing TPLO for cranial cruciate ligament rupture.

OBJECTIVE: The aim of this study was to evaluate the association between meniscal lesions and severity of osteoarthritis (OA) among dogs that underwent Tibial Plateau Leveling Osteotomy (TPLO) for stabilization of cranial cruciate ligament rupture (CrCLR) at the University of Tennessee in 2011-2017. RESULTS: There were a total of 252 meniscal tears. Factors associated with diagnosis of medial meniscal tears (MMT) in dogs were severe OA in comparison to no OA (3.8 OR, 2.0-8.0 95% CI, 0.001 p-value), sporting and mixed breed group compared to other breed (3.6 OR, 1.7-7.6 95% CI, 0.004 p-value; 3.2 OR, 1.6-6.6 95% CI, 0.019 p-value, respectively), increasing age (1.1 OR, 1.0-1.2 95% CI, 0.018 p-value), complete CrCLR compared to partial (3.3 OR, 2.1-5.0 95% CI, < 0.001 p-value), and arthrotomy compared to arthroscopy (2.2 OR, 1.4-3.1 95% CI, 0.002 p-value). The factors that did not have significance in predicting MMT were weight, sex, lameness period, and side affected.

Detection and analysis of tick-borne infections in communal dogs of northwest Zimbabwe.

Domestic dogs (Canis familiaris) may serve as a reservoir or a sentinel for infectious disease pathogens that can affect human and wildlife health. To understand the role of tick-borne diseases in rural and lesser developed regions, we investigated the prevalence of several tick-borne pathogens in communal dogs of Zimbabwe. Blood samples from 225 dogs in northwest Zimbabwe were assessed by serology for Ehrlichia canis, Anaplasma phagocytophilum and Borrelia burgdorferi, and 241 samples were assessed by polymerase chain reaction (PCR) for Ehrlichia. There was a high seroprevalence (73%) of E. canis-specific antibodies in domestic dogs in northwest Zimbabwe, but follow up analyses via PCR and genetic sequencing indicated only 7.5% of the canines were actively infected with the organism. Whilst indicating that an organism serologically related to E. canis is likely present in the region, this data also shows that the organism is currently present in a relative minority of the domestic dogs in the region. Its presence as evidenced by both serologic and PCR analysis is significant because of the 'one health' paradigm, where humans and wildlife may be affected by the exposure to this pathogen in domestic dogs.

Clitoral cyst in a bitch.

Clitoral cyst can be easily mistaken for a vaginal mass lesion and should be considered in the differential diagnosis for a female dog presenting with an anatomically abnormal external genital examination.

In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease.

Control of both tissue architecture and scale is a fundamental translational roadblock in tissue engineering. An experimental framework that enables investigation into how architecture and scaling may be coupled is needed. We fabricated a structurally organized engineered tissue unit that expanded in response to regenerative cues after implantation into mice with liver injury. Specifically, we found that tissues containing patterned human primary hepatocytes, endothelial cells, and stromal cells in a degradable hydrogel expanded more than 50-fold over the course of 11 weeks in mice with injured livers. There was a concomitant increase in graft function as indicated by the production of multiple human liver proteins. Histologically, we observed the emergence of characteristic liver stereotypical microstructures mediated by coordinated growth of hepatocytes in close juxtaposition with a perfused vasculature. We demonstrated the utility of this system for probing the impact of multicellular geometric architecture on tissue expansion in response to liver injury. This approach is a hybrid strategy that harnesses both biology and engineering to more efficiently deploy a limited cell mass after implantation.